This is a proposal to study the genetic control of tolerance to metals in the group IIb of the periodic chart and of a protein known to bind them, metallothionein (MT). The work will be done in Drosophila melanogaster. The properties and composition of MT will be studied in some detail to establish differences and similarities with mammalian MT. The synthesis of MT in response to cadmium will be analyzed and mutants with altered amounts (or properties) of this protein will be isolated. Study of these mutants will help elucidate the precise role of MT in the storage and metabolism of necessary metals such as zinc and in protection against such toxicologically powerful metals as cadmium and mercury. These elements are of great environmental health importance and understanding of their interactions with living organisms is necessary; expecially when such interactions may very well be similar in humans and other eukaryotes. The fact that the thionein gene may be directly inducible by metal cations makes it also a very interesting subject to study more general and basic questions related to the mechanisms of control of gene expression.